Division of Cardiovascular Diseases, Cardiovascular Research Institute, University of Kansas Medical Center, 3901 Rainbow Blvd, Rm. 1001 Eaton, MS 3006, Kansas City, KS 66160, USA.
Basic Res Cardiol. 2011 Sep;106(5):709-33. doi: 10.1007/s00395-011-0183-y. Epub 2011 May 4.
Hematopoietic cytokines, traditionally known to influence cellular proliferation, differentiation, maturation, and lineage commitment in the bone marrow, include granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor, stem cell factor, Flt-3 ligand, and erythropoietin among others. Emerging evidence suggests that these cytokines also exert multifarious biological effects on diverse nonhematopoietic organs and tissues. Although the precise mechanisms remain unclear, numerous studies in animal models of myocardial infarction (MI) and heart failure indicate that hematopoietic cytokines confer potent cardiovascular benefits, possibly through mobilization and subsequent homing of bone marrow-derived cells into the infarcted heart with consequent induction of myocardial repair involving multifarious mechanisms. In addition, these cytokines are also known to exert direct cytoprotective effects. However, results from small-scale clinical trials of G-CSF therapy as a single agent after acute MI have been discordant and largely disappointing. It is likely that cardiac repair following cytokine therapy depends on a number of known and unknown variables, and further experimental and clinical studies are certainly warranted to accurately determine the true therapeutic potential of such therapy. In this review, we discuss the biological features of several key hematopoietic cytokines and present the basic and clinical evidence pertaining to cardiac repair with hematopoietic cytokine therapy.
造血细胞因子，传统上被认为可以影响骨髓中的细胞增殖、分化、成熟和谱系定向，包括粒细胞集落刺激因子（G-CSF）、粒细胞-巨噬细胞集落刺激因子、干细胞因子、Flt-3 配体和促红细胞生成素等。新出现的证据表明，这些细胞因子也对多种非造血器官和组织发挥多样的生物学作用。尽管确切的机制尚不清楚，但心肌梗死（MI）和心力衰竭的动物模型中的大量研究表明，造血细胞因子具有强大的心血管益处，可能通过动员和随后骨髓源性细胞归巢到梗死心脏，从而诱导涉及多种机制的心肌修复。此外，这些细胞因子也已知具有直接的细胞保护作用。然而，急性 MI 后作为单一药物使用 G-CSF 治疗的小型临床试验结果存在差异，且大多令人失望。细胞因子治疗后的心脏修复可能取决于许多已知和未知的变量，因此，进一步的实验和临床研究肯定是必要的，以准确确定这种治疗的真正治疗潜力。在这篇综述中，我们讨论了几种关键造血细胞因子的生物学特征，并介绍了造血细胞因子治疗与心脏修复相关的基础和临床证据。
